Current Trends in Memory Implantation and Rehabilitation

  • Hyun Jae Jang
  • Sahn Woo Park
  • Jeehyun KwagEmail author
Part of the Trends in Augmentation of Human Performance book series (TAHP, volume 5)


Hippocampus is believed to be the brain region critical for memory storage and recall. Damage to the hippocampus by lesions or neurodegenerative diseases such as Alzheimer’s disease could lead to memory deficits. However, there is yet no treatment method available. Direct deep-brain stimulation (DBS) of the hippocampus has been attempted in an effort to find a treatment method for memory dysfunction and Alzheimer’s disease in the last few decades but with limited success. Recently, a novel approach has been developed where an implantation of a very large scale integration (VLSI) microchip containing a biomimetic computational model could act as an artificial bridge to replace the damaged hippocampal circuit in vivo. Here, we discuss the memory implantation techniques; from the conventional DBS method to the current memory implantation technology using an artificial neural microchip. Furthermore, we propose future directions towards the development of a physiologically realistic memory implantation chip design that could enhance the performance of the memory implant and be used for the treatment of memory-related neurodegenerative diseases.


Memory implantation Memory rehabilitation Hippocampus Synaptic plasticity Neuromorphic chip 


  1. 1.
    Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A 82:4245–4249PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Selkoe DJ (1994) Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer’s disease. Annu Rev Cell Biol 10:373–403CrossRefPubMedGoogle Scholar
  3. 3.
    Alzheimer’s A (2014) 2014 Alzheimer’s disease facts and figures. Alzheimers Dement 10:e47–e92CrossRefGoogle Scholar
  4. 4.
    Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M (2010) Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 9:702–716CrossRefPubMedGoogle Scholar
  5. 5.
    Halgren E, Wilson CL (1985) Recall deficits produced by afterdischarges in the human hippocampal formation and amygdala. Electroencephalogr Clin Neurophysiol 61:375–380CrossRefPubMedGoogle Scholar
  6. 6.
    Halgren E, Wilson CL, Stapleton JM (1985) Human medial temporal-lobe stimulation disrupts both formation and retrieval of recent memories. Brain Cogn 4:287–295CrossRefPubMedGoogle Scholar
  7. 7.
    Coleshill SG, Binnie CD, Morris RG, Alarcon G, van Emde Boas W, Velis DN et al (2004) Material-specific recognition memory deficits elicited by unilateral hippocampal electrical stimulation. J Neurosci 24:1612–1616CrossRefPubMedGoogle Scholar
  8. 8.
    Berger TW, Gerhardt G, Liker MA, Soussou W (2008) The impact of neurotechnology on rehabilitation. IEEE Rev Biomed Eng 1:157–197CrossRefPubMedGoogle Scholar
  9. 9.
    Berger TW, Hampson RE, Song D, Goonawardena A, Marmarelis VZ, Deadwyler SA (2011) A cortical neural prosthesis for restoring and enhancing memory. J Neural Eng 8:046017PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Hampson RE, Song D, Chan RH, Sweatt AJ, Riley MR, Goonawardena AV et al (2012) Closing the loop for memory prosthesis: detecting the role of hippocampal neural ensembles using nonlinear models. IEEE Trans Neural Syst Rehabil Eng 20:510–525PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Zola-Morgan S, Squire LR, Amaral DG (1986) Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J Neurosci 6:2950–2967PubMedGoogle Scholar
  12. 12.
    Andersen P, Bliss TV, Skrede KK (1971) Lamellar organization of hippocampal pathways. Exp Brain Res 13:222–238PubMedGoogle Scholar
  13. 13.
    Rempel-Clower NL, Zola SM, Squire LR, Amaral DG (1996) Three cases of enduring memory impairment after bilateral damage limited to the hippocampal formation. J Neurosci 16:5233–5255PubMedGoogle Scholar
  14. 14.
    Milner B, Taylor L, Sperry RW (1968) Lateralized suppression of dichotically presented digits after commissural section in man. Science 161:184–186CrossRefPubMedGoogle Scholar
  15. 15.
    Scoville WB, Milner B (1957) Loss of recent memory after bilateral hippocampal lesions. J Neurol Neurosurg Psychiatry 20:11–21PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39CrossRefPubMedGoogle Scholar
  17. 17.
    Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232:331–356PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Markram H, Lubke J, Frotscher M, Sakmann B (1997) Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275:213–215CrossRefPubMedGoogle Scholar
  19. 19.
    Bi GQ, Poo MM (1998) Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J Neurosci 18:10464–10472PubMedGoogle Scholar
  20. 20.
    Ito M, Kano M (1982) Long-lasting depression of parallel fiber-Purkinje cell transmission induced by conjunctive stimulation of parallel fibers and climbing fibers in the cerebellar cortex. Neurosci Lett 33:253–258CrossRefPubMedGoogle Scholar
  21. 21.
    Dudek SM, Bear MF (1992) Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc Natl Acad Sci U S A 89:4363–4367PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Bienenstock EL, Cooper LN, Munro PW (1982) Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J Neurosci 2:32–48PubMedGoogle Scholar
  23. 23.
    Wixted JT, Squire LR, Jang Y, Papesh MH, Goldinger SD, Kuhn JR et al (2014) Sparse and distributed coding of episodic memory in neurons of the human hippocampus. Proc Natl Acad Sci U S A 111:9621–9626PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Davis KD, Taub E, Houle S, Lang AE, Dostrovsky JO, Tasker RR et al (1997) Globus pallidus stimulation activates the cortical motor system during alleviation of Parkinsonian symptoms. Nat Med 3:671–674CrossRefPubMedGoogle Scholar
  25. 25.
    Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin C, Hoffmann D et al (1998) Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med 339:1105–1111CrossRefPubMedGoogle Scholar
  26. 26.
    Williams JM, Givens B (2003) Stimulation-induced reset of hippocampal theta in the freely performing rat. Hippocampus 13:109–116CrossRefPubMedGoogle Scholar
  27. 27.
    Ehret A, Haaf A, Jeltsch H, Heimrich B, Feuerstein TJ, Jackisch R (2001) Modulation of electrically evoked acetylcholine release in cultured rat septal neurones. J Neurochem 76:555–564CrossRefPubMedGoogle Scholar
  28. 28.
    Penfield W, Perot P (1963) The brain’s record of auditory and visual experience. A final summary and discussion. Brain 86:595–696CrossRefPubMedGoogle Scholar
  29. 29.
    Stone SS, Teixeira CM, Devito LM, Zaslavsky K, Josselyn SA, Lozano AM et al (2011) Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory. J Neurosci 31:13469–13484CrossRefPubMedGoogle Scholar
  30. 30.
    Toda H, Hamani C, Fawcett AP, Hutchison WD, Lozano AM (2008) The regulation of adult rodent hippocampal neurogenesis by deep brain stimulation. J Neurosurg 108:132–138CrossRefPubMedGoogle Scholar
  31. 31.
    Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C et al (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45:651–660CrossRefPubMedGoogle Scholar
  32. 32.
    Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH (2008) Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 64:461–467CrossRefPubMedGoogle Scholar
  33. 33.
    Suthana N, Haneef Z, Stern J, Mukamel R, Behnke E, Knowlton B et al (2012) Memory enhancement and deep-brain stimulation of the entorhinal area. N Engl J Med 366:502–510PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Hardenacke K, Shubina E, Buhrle CP, Zapf A, Lenartz D, Klosterkotter J et al (2013) Deep brain stimulation as a tool for improving cognitive functioning in Alzheimer’s dementia: a systematic review. Front Psychiatry 4:159PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Suthana N, Fried I (2014) Deep brain stimulation for enhancement of learning and memory. Neuroimage 85(3):996–1002PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Hampson RE, Song D, Opris I, Santos LM, Shin DC, Gerhardt GA et al (2013) Facilitation of memory encoding in primate hippocampus by a neuroprosthesis that promotes task-specific neural firing. J Neural Eng 10:066013PubMedCentralCrossRefPubMedGoogle Scholar
  37. 37.
    Gaffan D (1974) Recognition impaired and association intact in the memory of monkeys after transection of the fornix. J Comp Physiol Psychol 86:1100–1109CrossRefPubMedGoogle Scholar
  38. 38.
    Mishkin M (1978) Memory in monkeys severely impaired by combined but not by separate removal of amygdala and hippocampus. Nature 273:297–298CrossRefPubMedGoogle Scholar
  39. 39.
    Song D, Chan RH, Marmarelis VZ, Hampson RE, Deadwyler SA, Berger TW (2009) Nonlinear modeling of neural population dynamics for hippocampal prostheses. Neural Netw 22:1340–1351PubMedCentralCrossRefPubMedGoogle Scholar
  40. 40.
    Berger TW, Song D, Chan RH, Marmarelis VZ, LaCoss J, Wills J et al (2012) A hippocampal cognitive prosthesis: multi-input, multi-output nonlinear modeling and VLSI implementation. IEEE Trans Neural Syst Rehabil Eng 20:198–211PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Song D, Chan RH, Marmarelis VZ, Hampson RE, Deadwyler SA, Berger TW (2007) Nonlinear dynamic modeling of spike train transformations for hippocampal-cortical prostheses. IEEE Trans Biomed Eng 54:1053–1066CrossRefPubMedGoogle Scholar
  42. 42.
    Hampson RE, Gerhardt GA, Marmarelis V, Song D, Opris I, Santos L et al (2012) Facilitation and restoration of cognitive function in primate prefrontal cortex by a neuroprosthesis that utilizes minicolumn-specific neural firing. J Neural Eng 9:056012PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Deadwyler SA, Berger TW, Sweatt AJ, Song D, Chan RH, Opris I et al (2013) Donor/recipient enhancement of memory in rat hippocampus. Front Syst Neurosci 7:120PubMedCentralCrossRefPubMedGoogle Scholar
  44. 44.
    Song D, Harway M, Marmarelis VZ, Hampson RE, Deadwyler SA, Berger TW (2014) Extraction and restoration of hippocampal spatial memories with non-linear dynamical modeling. Front Syst Neurosci 8:97PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Rosin B, Slovik M, Mitelman R, Rivlin-Etzion M, Haber SN, Israel Z et al (2011) Closed-loop deep brain stimulation is superior in ameliorating parkinsonism. Neuron 72:370–384CrossRefPubMedGoogle Scholar
  46. 46.
    Santos FJ, Costa RM, Tecuapetla F (2011) Stimulation on demand: closing the loop on deep brain stimulation. Neuron 72:197–198CrossRefPubMedGoogle Scholar
  47. 47.
    Jarosiewicz B, Masse NY, Bacher D, Cash SS, Eskandar E, Friehs G et al (2013) Advantages of closed-loop calibration in intracortical brain-computer interfaces for people with tetraplegia. J Neural Eng 10:046012PubMedCentralCrossRefPubMedGoogle Scholar
  48. 48.
    Robinson BS, Song D, Berger TW (2013) Laguerre-Volterra identification of spike-timing-dependent plasticity from spiking activity: a simulation study. Conf Proc IEEE Eng Med Biol Soc 2013:5578–5581PubMedGoogle Scholar
  49. 49.
    Dong S, Robinson BS, Granacki JJ, Berger TW (2014) Implementing spiking neuron model and spike-timing-dependent plasticity with generalized Laguerre-Volterra models. Conf Proc IEEE Eng Med Biol Soc 2014:714–717Google Scholar
  50. 50.
    Sjostrom PJ, Turrigiano GG, Nelson SB (2001) Rate, timing, and cooperativity jointly determine cortical synaptic plasticity. Neuron 32:1149–1164CrossRefPubMedGoogle Scholar
  51. 51.
    Froemke RC, Dan Y (2002) Spike-timing-dependent synaptic modification induced by natural spike trains. Nature 416:433–438CrossRefPubMedGoogle Scholar
  52. 52.
    Wang HX, Gerkin RC, Nauen DW, Bi GQ (2005) Coactivation and timing-dependent integration of synaptic potentiation and depression. Nat Neurosci 8:187–193CrossRefPubMedGoogle Scholar
  53. 53.
    Froemke RC, Poo MM, Dan Y (2005) Spike-timing-dependent synaptic plasticity depends on dendritic location. Nature 434:221–225CrossRefPubMedGoogle Scholar
  54. 54.
    Woodin MA, Ganguly K, Poo MM (2003) Coincident pre- and postsynaptic activity modifies GABAergic synapses by postsynaptic changes in Cl- transporter activity. Neuron 39:807–820CrossRefPubMedGoogle Scholar
  55. 55.
    Lamsa KP, Kullmann DM, Woodin MA (2010) Spike-timing dependent plasticity in inhibitory circuits. Front Synaptic Neurosci 2:8PubMedCentralPubMedGoogle Scholar
  56. 56.
    Somogyi P, Klausberger T (2005) Defined types of cortical interneurone structure space and spike timing in the hippocampus. J Physiol 562:9–26PubMedCentralCrossRefPubMedGoogle Scholar
  57. 57.
    Klausberger T, Somogyi P (2008) Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 321:53–57PubMedCentralCrossRefPubMedGoogle Scholar
  58. 58.
    Saraga F, Balena T, Wolansky T, Dickson CT, Woodin MA (2008) Inhibitory synaptic plasticity regulates pyramidal neuron spiking in the rodent hippocampus. Neuroscience 155:64–75CrossRefPubMedGoogle Scholar
  59. 59.
    Rubin JE, Gerkin RC, Bi GQ, Chow CC (2005) Calcium time course as a signal for spike-timing-dependent plasticity. J Neurophysiol 93:2600–2613CrossRefPubMedGoogle Scholar
  60. 60.
    Urakubo H, Honda M, Froemke RC, Kuroda S (2008) Requirement of an allosteric kinetics of NMDA receptors for spike timing-dependent plasticity. J Neurosci 28:3310–3323CrossRefPubMedGoogle Scholar
  61. 61.
    Hasselmo ME, Schnell E, Barkai E (1995) Dynamics of learning and recall at excitatory recurrent synapses and cholinergic modulation in rat hippocampal region CA3. J Neurosci 15:5249–5262PubMedGoogle Scholar
  62. 62.
    Cutsuridis V, Cobb S, Graham BP (2010) Encoding and retrieval in a model of the hippocampal CA1 microcircuit. Hippocampus 20:423–446PubMedGoogle Scholar
  63. 63.
    Rachmuth G, Shouval HZ, Bear MF, Poon CS (2011) A biophysically-based neuromorphic model of spike rate- and timing-dependent plasticity. Proc Natl Acad Sci U S A 108:E1266–E1274PubMedCentralCrossRefPubMedGoogle Scholar
  64. 64.
    Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K et al (2012) Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484:381–385PubMedCentralCrossRefPubMedGoogle Scholar
  65. 65.
    Ramirez S, Liu X, Lin PA, Suh J, Pignatelli M, Redondo RL et al (2013) Creating a false memory in the hippocampus. Science 341:387–391CrossRefPubMedGoogle Scholar
  66. 66.
    Liu X, Ramirez S, Tonegawa S (2014) Inception of a false memory by optogenetic manipulation of a hippocampal memory engram. Philos Trans R Soc Lond B Biol Sci 369:20130142PubMedCentralCrossRefPubMedGoogle Scholar
  67. 67.
    Boggio PS, Ferrucci R, Mameli F, Martins D, Martins O, Vergari M et al (2012) Prolonged visual memory enhancement after direct current stimulation in Alzheimer’s disease. Brain Stimul 5:223–230CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Department of Brain and Cognitive EngineeringKorea UniversitySeoulRepublic of Korea

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